生物
转移
结直肠癌
原发性肿瘤
乳腺癌
外显子组测序
外显子组
癌症的体细胞进化
癌症
转移性乳腺癌
肿瘤科
癌变
癌症研究
内科学
突变
遗传学
基因
医学
作者
Zheng Hu,Zan Li,Zhicheng Ma,Christina Curtis
出处
期刊:Nature Genetics
[Springer Nature]
日期:2020-05-18
卷期号:52 (7): 701-708
被引量:194
标识
DOI:10.1038/s41588-020-0628-z
摘要
Metastasis is the primary cause of cancer-related deaths, but the natural history, clonal evolution and impact of treatment are poorly understood. We analyzed whole-exome sequencing (WES) data from 457 paired primary tumor and metastatic samples from 136 patients with breast, colorectal and lung cancer, including untreated (n = 99) and treated (n = 100) metastases. Treated metastases often harbored private 'driver' mutations, whereas untreated metastases did not, suggesting that treatment promotes clonal evolution. Polyclonal seeding was common in untreated lymph node metastases (n = 17 out of 29, 59%) and distant metastases (n = 20 out of 70, 29%), but less frequent in treated distant metastases (n = 9 out of 94, 10%). The low number of metastasis-private clonal mutations is consistent with early metastatic seeding, which we estimated occurred 2-4 years before diagnosis across these cancers. Furthermore, these data suggest that the natural course of metastasis is selectively relaxed relative to early tumorigenesis and that metastasis-private mutations are not drivers of cancer spread but instead associated with drug resistance.
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